title: Glutamine supplementation, but not combined glutamine and arginine supplementation, improves gut barrier function during chemotherapy-induced intestinal mucositis in rats.
abstract: OBJECTIVE
  Increased intestinal permeability occurs during chemotherapy-induced intestinal mucositis. Previous data suggest that glutamine and arginine may have additive or synergic effects to limit intestinal damage. The present study aimed to evaluate the effects of glutamine and arginine, each alone or in combination, on gut barrier function during methotrexate (MTX)-induced mucositis in rats.
  
  
  METHODS
  Eighty Sprague Dawley rats received during 7 days (d) standard chow supplemented with protein powder (PP), glutamine (G, 2%), arginine (A, 1.2%) or glutamine plus arginine (GA). All diets were isonitrogenous. Rats received subcutaneous injections of MTX (2.5 mg/kg) from d0 to d2. The intestinal permeability and tight junction proteins were assessed at d4 and d9 in the jejunum by FITC-dextran and by western blot and immunohistochemistry, respectively.
  
  
  RESULTS
  At d4, intestinal permeability was increased in MTX-PP, MTX-A and MTX-GA rats compared with controls but not in MTX-G rats. The expression of claudin-1, occludin and ZO-1 was decreased in MTX-PP group compared with controls but was restored in MTX-G and MTX-A rats. In MTX-GA rats, occludin expression remained decreased. These effects could be explained by an increase of erk phosphorylation and a decrease of IκBα expression in MTX-PP and MTX-GA rats. At d9, Intestinal permeability remained higher only in MTX-GA rats. This was associated with a persistent decrease of occludin expression.
  
  
  CONCLUSIONS
  Glutamine prevents MTX-induced gut barrier disruption by regulating occludin and claudin-1 probably through erk and NF-κB pathways. In contrast, combined glutamine and arginine has no protective effect in this model.
authors.affiliation: INSERM Unit 1073, Rouen University, Rouen, France; Institute for Research and Innovation in Biomedicine, Rouen University, Rouen, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Beutheu
authors.affiliation: INSERM Unit 1073, Rouen University, Rouen, France; Institute for Research and Innovation in Biomedicine, Rouen University, Rouen, France.
authors.forename: Wassila
authors.initials: W
authors.lastname: Ouelaa
authors.affiliation: INSERM Unit 1073, Rouen University, Rouen, France; Institute for Research and Innovation in Biomedicine, Rouen University, Rouen, France.
authors.forename: Charlène
authors.initials: C
authors.lastname: Guérin
authors.affiliation: INSERM Unit 1073, Rouen University, Rouen, France; Institute for Research and Innovation in Biomedicine, Rouen University, Rouen, France.
authors.forename: Liliana
authors.initials: L
authors.lastname: Belmonte
authors.affiliation: Laboratory of Anatomopathology, Rouen University Hospital, Rouen, France.
authors.forename: Moutaz
authors.initials: M
authors.lastname: Aziz
authors.affiliation: INSERM Unit 1073, Rouen University, Rouen, France; Institute for Research and Innovation in Biomedicine, Rouen University, Rouen, France.
authors.forename: Naouel
authors.initials: N
authors.lastname: Tennoune
authors.affiliation: INSERM Unit 1073, Rouen University, Rouen, France; Institute for Research and Innovation in Biomedicine, Rouen University, Rouen, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Bôle-Feysot
authors.affiliation: Institute for Research and Innovation in Biomedicine, Rouen University, Rouen, France; PRIMACEN, Cell Imaging Platform of Normandy, Rouen University, Mont Saint Aignan, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Galas
authors.affiliation: INSERM Unit 1073, Rouen University, Rouen, France; Institute for Research and Innovation in Biomedicine, Rouen University, Rouen, France; Nutrition Unit, Rouen University Hospital, Rouen, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Déchelotte
authors.affiliation: INSERM Unit 1073, Rouen University, Rouen, France; Institute for Research and Innovation in Biomedicine, Rouen University, Rouen, France; Nutrition Unit, Rouen University Hospital, Rouen, France. Electronic address: moise.coeffier@univ-rouen.fr.
authors.forename: Moïse
authors.initials: M
authors.lastname: Coëffier
mesh_terms: D000818:Animals; D001120:Arginine / Q000008:administration & dosage; D019587:Dietary Supplements; D004195:Disease Models, Animal; D041981:Gastrointestinal Tract; D005973:Glutamine / Q000008:administration & dosage*; D007150:Immunohistochemistry; D007422:Intestines / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008727:Methotrexate / Q000009:adverse effects; D052016:Mucositis / Q000139:chemically induced / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D062793:Occludin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016328:NF-kappa B; D062793:Occludin; D012333:RNA, Messenger; D005973:Glutamine; D001120:Arginine; D008727:Methotrexate
keywords: Arginine; Chemotherapy; Glutamine; Gut barrier; Signaling pathways